Vascular endothelial growth factor is neuroprotective against ischemic brain injury by inhibiting scavenger receptor A expression on microglia

Xu, Zheng; Han, Kaiwei; Chen, Jigang; Wang, Chunhui; Dong, Yan; Yu, Min; Bai, Rulin; Huang, Chenguang; Hou, Lingling

doi:10.1111/jnc.14108

Cited by 32 publications

(21 citation statements)

References 45 publications

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“…These inflammatory factors are thought to contribute to post‐ischaemic neuronal damage and apoptosis, so worsening the outcome after stroke . Furthermore, genetic or pharmacological inhibition of certain microglial functions, such as proliferation and release of cytokines, may result in dampened inflammatory responses and neuronal damage after ischaemic insult . Importantly, factors such as Fas ligand released by ischaemic neurons may induce a specific pro‐inflammatory phenotype in microglia .…”

Section: Innate Immune Responses To Ischaemic Injuries Within the Cenmentioning

confidence: 99%

“…16 Furthermore, genetic or pharmacological inhibition of certain microglial functions, such as proliferation and release of cytokines, may result in dampened inflammatory responses and neuronal damage after ischaemic insult. [20][21][22][23] Importantly, factors such as Fas ligand released by ischaemic neurons may induce a specific pro-inflammatory phenotype in microglia. 24 A recent study by Meng et al suggests that neuronal soluble Fas ligand promotes microglial polarization to the 'M1' classical activation phenotype after cerebral ischaemia; and that 'M1-microglia' release pro-inflammatory factors leading to reduced cell viability and survival.…”

Section: Introductionmentioning

confidence: 99%

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Immune responses in stroke: how the immune system contributes to damage and healing after stroke and how this knowledge could be translated to better cures?

et al. 2018

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Stroke is one of the leading causes of death and disability worldwide. The long-standing dogma that stroke is exclusively a vascular disease has been questioned by extensive clinical findings of immune factors that are associated mostly with inflammation after stroke. These have been confirmed in preclinical studies using experimental animal models. It is now accepted that inflammation and immune mediators are critical in acute and long-term neuronal tissue damage and healing following thrombotic and ischaemic stroke. Despite mounting information delineating the role of the immune system in stroke, the mechanisms of how inflammatory cells and their mediators are involved in stroke-induced neuroinflammation are still not fully understood. Currently, there is no available treatment for targeting the acute immune response that develops in the brain during cerebral ischaemia. No new treatment has been introduced to stroke therapy since the discovery of tissue plasminogen activator therapy in 1996. Here, we review current knowledge of the immunity of stroke and identify critical gaps that hinder current therapies. We will discuss advances in the understanding of the complex innate and adaptive immune responses in stroke; mechanisms of immune cell-mediated and factor-mediated vascular and tissue injury; immunity-induced tissue repair; and the importance of modulating immunity in stroke.

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Section: Innate Immune Responses To Ischaemic Injuries Within the Cenmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immune responses in stroke: how the immune system contributes to damage and healing after stroke and how this knowledge could be translated to better cures?

et al. 2018

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“…5C). VEGF suppresses inflammatory brain response [38] and reduces neurodegeneration in mouse models of AD [39,40].…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism and endocannabinoid signaling

Asaro

Carlo-Spiewok

Malik

et al. 2020

Preprint

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INTRODUCTION, ApoE is a carrier for brain lipids and the most important genetic risk factor for Alzheimer's disease (AD). ApoE binds the receptor sortilin which mediates uptake of apoE-bound cargo into neurons. The significance of this uptake route for brain lipid homeostasis and AD risk seen with apoE4, but not apoE3, remains unresolved.METHODS, Combining neurolipidomics in patient specimens with functional studies in mouse models, we interrogated apoE isoform-specific functions for sortilin in brain lipid metabolism and AD.RESULTS, Sortilin directs uptake and conversion of polyunsaturated fatty acids into endocannabinoids, lipid-based neurotransmitters that act through nuclear receptors to sustain neuroprotective gene expression in the brain. This sortilin function requires apoE3, but is disrupted by binding of apoE4, impairing endocannabinoid signaling and increasing amyloidogenic processing. DISCUSSION, We uncovered the significance of neuronal apoE receptor sortilin in facilitating neuroprotective actions of brain lipids, and its relevance for AD risk seen with apoE4.

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“…Hif1α ‐regulated genes include VEGF and EPO as well as endothelial nitric oxide synthase, and VEGF and EPO have been shown to function as neuroprotective molecules in HI models and in clinical trials in neonatal mice and infants (Nowacka and Obuchowicz, ; Song et al, ; Xu et al, ). In this study, AQ administration increased the expression of Hif1α in HI‐induced brain injury, and this increase was more obvious in males.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in neonatal mouse brain injury after hypoxia‐ischemia and adaptaquin treatment

Wang

et al. 2019

Journal of Neurochemistry

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Hypoxia‐inducible factor prolyl 4‐hydroxylases (HIF‐PHDs) are important targets against oxidative stress. We hypothesized that inhibition HIF‐PHD by adaptaquin reduces hypoxic‐ischemic brain injury in a neonatal mouse model. The pups were treated intraperitoneally immediately with adaptaquin after hypoxia‐ischemia (HI) and then every 24 h for 3 days. Adaptaquin treatment reduced infarction volume by an average of 26.3% at 72 h after HI compared to vehicle alone, and this reduction was more pronounced in males (34.8%) than in females (11.7%). The protection was also more pronounced in the cortex. The subcortical white matter injury as measured by tissue loss volume was reduced by 24.4% in the adaptaquin treatment group, and this reduction was also more pronounced in males (28.4%) than in females (18.9%). Cell death was decreased in the cortex as indicated by Fluoro‐Jade labeling, but not in other brain regions with adaptaquin treatment. Furthermore, in the brain injury area, adaptaquin did not alter the number of cells positive for caspase‐3 activation or translocation of apoptosis‐inducing factor to the nuclei. Adaptaquin treatment increased glutathione peroxidase 4 mRNA expression in the cortex but had no impact on 3‐nitrotyrosine, 8‐hydroxy‐2 deoxyguanosine, or malondialdehyde production. Hif1α mRNA expression increased after HI, and adaptaquin treatment also stimulated Hif1α mRNA expression, which was also more pronounced in males than in females. However, nuclear translocation of HIF1α protein was decreased after HI, and adaptaquin treatment had no influence on HIF1α expression in the nucleus. These findings demonstrate that adaptaquin treatment is neuroprotective, but the potential mechanisms need further investigation. Read the Editorial Highlight for this article on page 645.

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Vascular endothelial growth factor is neuroprotective against ischemic brain injury by inhibiting scavenger receptor A expression on microglia

Cited by 32 publications

References 45 publications

Immune responses in stroke: how the immune system contributes to damage and healing after stroke and how this knowledge could be translated to better cures?

Immune responses in stroke: how the immune system contributes to damage and healing after stroke and how this knowledge could be translated to better cures?

Apolipoprotein E4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism and endocannabinoid signaling

Sex differences in neonatal mouse brain injury after hypoxia‐ischemia and adaptaquin treatment

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